Mast cell activation in murine EAE

M A S T CELL ACTIVATION IN MURINE EAE W . K r e n g e r , D. Yasui, A. AI-Sabbagh, °S. S r i r a m and D. Johnson. Center for Neurologic Diseases, Brigham and Women's Hospital. Boston, MA, USA; and *University of Vermont, Burlington, VT, USA. In order to extend our studies on the role of mast cells in the pathogenesis of EAE, we have examine passive and active disease in the SJL/J mouse. Toluidine blue staining of brains of mice with EAE induced by adoptive transfer of basic protein (BP)-sensitised T cells showed a significant increase in periventricular mast cell number, compared to untreated controls. Th ~,~emast cells were clustered around blood vessels, and some appeared degranulated. A similar pattern was observed in the CNS of mice with EAE that had been actively induced with whole myelin. Scauning electron microscopy of these brains confirmed de identity of the mast cells, and showed them to be closely associated with infiltrating lymphocytes. Culture supernatants from BP-specific T cells caused a marked proliferation of both mast cell lines (MC/9) and primary cultures of bone marrow-derived mast cells. While neutralising antibodies to IL-3 were unable to block the stimulation of the MC/9 proliferation, they completely inhibited the increase in proliferation of the primary mast cell cultures. Thus the increased numbers of CNS mast cells we observe in EAE may be due tG IL-3 production by activated T cells.

PASSIVE T R A N S F E R EAE A N D T-CELL REPERTOIRE IN PRIMATES Massacesi L., N. Joshi, D.L. Parritz, D. Can-field, N.L. Letvin and S.L. Hauser. Neuroim-munology Unit, Mass. Gen. Hospital, Boston, USA. Callitrix Jaccos new world monkeys (marmoset) are born as non identical twins or triplets that in utero share a common circulation, generating a permanent stable bone marrow chimeric state. Chronic relapsing EAE was induced in this primate following immunization with human white matter. The disease was characterized by slowly evolving and mild neurological signs and pathologically by perivascular mononuclear cell infiltrates with demyelination and astrogliosis. This picture is similar to what has been described as "macrophage mediated demyelination" without the hemorragic and polimorphonuclear cell infiltrates characteristic of more acute form of primate EAE. The natural chimeric state made possible the passive transfer of EAE between non identical twins. MBP-reactive Tcell lines were generated from spleen cells and lymphnodes collected from donors which developed active EAE and a chronic relapsing form of passive EAE was induced by passive transfer of these lines. The encephalitogenic CD4+fI'NF expressing lines recognized different regions of MBP, indicating that in marmoset reactivity to MBP is not restricted to a single immunodominant epitope.